Typically, cells are cultured in vitro by growing cells in a fluid or gel-like growth media in a sterile container under certain controlled conditions, including the temperature and pH. In many stem cell cultures, for example, cells are grown as free-floating aggregates in suspension in a media. However, in such cultures, the immediate vicinity of a cell, its microenvironment, is constantly changing such that a cell is exposed to a variable and uncontrolled local environment, which may not closely resemble the cell's in vivo environment. This results in a heterogenous mixture of cell types, even in cultures started with a single cell. The
In vivo, molecules secreted by cells are important for their function and the function of neighbouring cells. However, in known culture systems, these molecules quickly diffuse away and are diluted such that the interactions of cells with locally-secreted molecules that occur in vivo is lost or is ineffective and one or more of the cells' normal functions thus may be affected. Additionally, in some traditional cell cultures cells tend to attach or adhere to the surface of the cell culture container, which may not be desirable for some cell types. For example, attachment of many stem or progenitor cells may not be desirable as it may promote differentiation and otherwise change the cell phenotype.
In known in vitro or ex vivo cell culture methods and apparatus it is difficult or impossible to control the properties and phenotype of individual cells, to trace cell division and lineage, and to monitor and record activity (behaviour) histories for each individual cell within the culture. Some conventional techniques for obtaining high resolution images of cultured cells, such as laser scanning confocal microscopy, are not suitable for long-term imaging of cultured cells. For example, in conventional high resolution imaging techniques such as laser scanning confocal microscopy, the cultured cells are usually exposed to high intensity light. As a result, light- or laser-induced phototoxicity can limit the time during which a live cell can be imaged. Further, it is generally expensive to obtain high resolution images of cells cultured using conventional techniques.
Therefore there is a need for increased control of a cell culture.